Testosterone Replacement Therapy (TRT) is a common treatment for men with hypogonadism, a condition where the body does not produce enough testosterone. While TRT is primarily known for improving symptoms like fatigue, reduced muscle mass, and sexual dysfunction, emerging research suggests that TRT may also play a role in managing anemia in men with low testosterone, particularly as they age. The connection between testosterone, anemia, and aging is becoming a topic of significant interest, as evidenced by recent findings from large clinical trials like the TRAVERSE study.
(Credit: The Lancet)
Prevalence of Hypogonadism and Anemia in Aging Men
Low testosterone levels are prevalent among aging men. According to the Massachusetts Male Aging Study (MMAS), approximately 25.3% of men between 40 and 70 have low testosterone based on blood tests alone (SpringerLink).
Hypogonadism, which includes both low testosterone and specific symptoms, affects around 6% to 12% of men in this age group (SpringerLink).
Symptoms such as reduced libido, fatigue, and decreased muscle mass are common in men with hypogonadism, and anemia is also frequently observed in this population.
Anemia in older adults is often mild and categorized as normocytic, meaning the red blood cells are of normal size but fewer in number. The prevalence of anemia in aging men can be as high as 15%, with about 10% to 15% of these men having both anemia and low testosterone levels (Lifespan Health).
The underlying mechanisms are complex, but testosterone has been shown to influence hemoglobin production, which is crucial for oxygen transport in the blood.
The TRAVERSE Trial: Testosterone and Anemia
A pivotal study published in JAMA Network Open in 2023 by Pencina et al. examined the effects of TRT on anemia among men with hypogonadism. The TRAVERSE trial followed over 5,000 men aged 45 to 80 years for up to four years, providing significant insights into how TRT may improve hemoglobin levels and reduce the prevalence of anemia (SpringerLink).
Key Findings:
- Correction of Anemia: At baseline, 15.7% of men in the study had anemia (hemoglobin levels below 12.7 g/dL). TRT corrected anemia in 10% to 15% more men compared to those receiving a placebo within the first six months (SpringerLink) (Lifespan Health). However, there was a slight decline in the benefits over time.
- Prevention of New Anemia: TRT also prevented the development of new cases of anemia in 2% to 3% of men who did not have anemia at the start of the trial. While the absolute changes in hemoglobin were relatively small (~0.3 g/dL), the prevention of anemia adds another potential benefit of TRT (SpringerLink).
- Impact on Symptoms: The trial also assessed self-reported energy and fatigue using the Hypogonadism Impact of Symptoms Questionnaire. Unfortunately, the improvements in these areas were modest, and no significant effect on cognitive function was noted (Lifespan Health). However, TRT did improve hemoglobin levels without significantly increasing the risk of major cardiovascular events.
Mechanisms: How Testosterone Affects Hemoglobin Levels
Testosterone plays a crucial role in stimulating the production of erythropoietin, a hormone that promotes red blood cell production. Low testosterone can lead to decreased erythropoietin levels, which in turn reduces hemoglobin and red blood cell count, resulting in anemia. TRT helps restore testosterone levels, which subsequently stimulates erythropoiesis, the process of producing red blood cells (Lifespan Health).
Moreover, studies have demonstrated that castration (medical or surgical), commonly used in treating prostate cancer, results in a rapid decline in hemoglobin by 0.7 to 1.6 g/L within three to six months (Lifespan Health). This suggests that testosterone levels are closely tied to maintaining normal male hemoglobin production.
Safety and Risks of TRT
While TRT offers clear benefits in treating hypogonadism and improving bone density, sexual function, and potentially anemia, concerns remain about its safety. The 2023 TRAVERSE trial provides some reassurance, showing no significant increase in major adverse cardiovascular events (MACE) or venous thromboembolism in men receiving TRT compared to the placebo group (SpringerLink). However, there was a slight trend toward an increased incidence of non-fatal cardiac arrhythmias and acute kidney injury in men treated with TRT, though these findings require further investigation (Lifespan Health).
Clinical Implications: Is TRT Right for You?
The TRAVERSE trial provides valuable data on TRT’s ability to manage anemia in hypogonadal men. However, it’s important to note that TRT should not be prescribed solely to treat asymptomatic anemia. The 2018 Endocrine Society guidelines recommend TRT only after a thorough evaluation of the potential risks and benefits, especially in older men with low testosterone (Lifespan Health).
Men with symptomatic hypogonadism can expect small increases in hemoglobin levels and possibly modest improvements in energy if they have anemia. However, improvements in cognition or overall well-being are unlikely based on current evidence. Before starting TRT, patients should have a complete work-up to rule out other causes of anemia and monitor prostate-specific antigen (PSA) levels to ensure prostate health (Lifespan Health).
Conclusion: A Balanced Approach to Testosterone Replacement
TRT offers a promising solution for managing anemia in men with hypogonadism, in addition to improving sexual function and bone density. While the benefits for anemia are modest, TRT may help correct mild anemia in up to 15% of men and prevent its onset in others. As with any medical treatment, carefully considering the risks and benefits is crucial.
For more information on testosterone therapy and whether it’s right for you, book a free call with a 1st Optimal care team member. Always consult a 1st Optimal Physician to discuss your individual health needs and to ensure a personalized approach to treatment.
